A nationwide blood spot screening study for Fabry disease in the Czech Republic haemodialysis patient population

Background. Fabry disease (FD) is a genetic disorder characterized by accumulation of trihexosylceramide in lysosomes of various tissues leading to multiorgan manifestations, including progressive renal disease. Previous screening studies have shown that a non-neglectable proportion of haemodialysis...

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Published in:	Nephrology, dialysis, transplantation Vol. 22; no. 1; pp. 179 - 186
Main Authors:	Merta, Miroslav, Reiterova, Jana, Ledvinova, Jana, Poupětová, Helena, Dobrovolný, Robert, Ryšavá, Romana, Maixnerová, Dita, Bultas, Jan, Motáň, Jiří, Slivkova, Jitka, Sobotova, Doris, Smrzova, Jana, Tesař, Vladimir
Format:	Journal Article
Language:	English
Published:	Oxford Oxford University Press 01-01-2007 Oxford Publishing Limited (England)
Subjects:	Adult Aged alpha-Galactosidase - chemistry Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Biological and medical sciences blood spot screening Czech Republic Emergency and intensive care: renal failure. Dialysis management end-stage renal disease enzyme replacement therapy Enzymes - therapeutic use Fabry disease Fabry Disease - blood Fabry Disease - diagnosis Fabry Disease - therapy Female haemodialysis Humans Intensive care medicine Lysosomes - metabolism Male Medical sciences Middle Aged Nephrology. Urinary tract diseases Nephropathies. Renovascular diseases. Renal failure Pedigree Protein Conformation Renal Dialysis - methods Renal failure Spectrometry, Fluorescence Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the urinary system α-galactosidase A Czech Republic Europe Fabry disease haemodialysis blood spot screening α-galactosidase A enzyme replacement therapy end-stage renal disease Kidney disease Human Nervous system diseases Replacement therapy Urinary system disease Hemodialysis Cardiovascular disease Metabolic diseases Lipids Terminal stage Medical screening Enzymopathy Genetic disease Vascular disease Extrarenal dialysis Renal failure Lipoidosis
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Summary:	Background. Fabry disease (FD) is a genetic disorder characterized by accumulation of trihexosylceramide in lysosomes of various tissues leading to multiorgan manifestations, including progressive renal disease. Previous screening studies have shown that a non-neglectable proportion of haemodialysis(HD) patients have unsuspected FD. An extensive FD screening study, the largest to date, has been conducted in HD patients in Czech Republic. We aimed to uncover previously undiagnosed FD patients, to enable them to benefit from cause-specific therapeutic intervention with enzyme replacement therapy (ERT). Methods. Large-scale screening was executed using a convenient automated enzymatic (α-galactosidose A, α-Gal A) dried blood spot on filter paper fluorescence method. Results. In total, 3370 (45.1% males, 54.9% females) out of 4058 HD patients (83%) in Czech Republic participated in this blood spot screening (BSS) study. Abnormal low fluorescence readings were obtained in 117 patients (3.5%). Subsequent determination of plasma α-Gal A activity identified four males and three females with deficient plasma enzyme activity. Determination of α-Gal A activity in peripheral blood leucocytes and confirmatory molecular analysis resulted in four newly diagnosed Fabry males and one female. Subsequent family screening identified 10 family members with genotypically proven FD. Based on these screening results, ERT could be offered to five male FD patients. Conclusions. BSS represents a promising screening tool that has proven to be convenient and effective in uncovering unrecognized FD patients among the chronic HD population in Czech Republic.
Bibliography:	ark:/67375/HXZ-5T17CZ4T-M istex:8F9CC5F7B27B1D02645A45793C281E5260755D3F ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0931-0509 1460-2385
DOI:	10.1093/ndt/gfl528